Today’s glaucoma therapy: Vitamins enter the arena, first-line pharmaceutical options shift

Issue: February 2000

Medical and surgical options for glaucoma treatment continue to expand and shift. As new therapeutic options become available, many practitioners still hesitate to reach for beta-blockers as a first-line treatment. And in some cases when clinicians may be unsuccessful with traditional treatment, they and their patients are beginning to seek a more holistic approach and are investigating nutritional alternatives for therapy.

Because glaucoma is influenced by vascular status, some practitioners advocate the use of nutritional supplements for patients suffering from open-angle glaucoma. However, others are still not convinced of the benefits.

“There is little scientific evidence that supplemental nutritional support has anything to do with glaucoma,” said Jimmy D. Bartlett, OD, professor of optometry, School of Optometry and professor of pharmacology, School of Medicine, at the University of Alabama at Birmingham. “There is some supposition and hypothesis, and you’d think that maybe by increasing blood flow we might be able to augment the health of the optic nerve tissues or retinal ganglion cell layer. There is some evidence that possibly contrast sensitivity improvements in glaucoma may be related to blood flow, but all of that needs further clarification at this point.”

Vitamin supplements: Ginkgo biloba

Many practitioners believe that a healthy vascular status is important to the prevention and possible treatment of glaucoma. “The three factors in glaucoma are intraocular pressure, circulation in the back of the nerve and the neuroprotective factor,” said Rob Abel, MD, one of 10 practitioners at Delaware Ophthalmology Consultants in Wilmington, Del. “Dr. Robert Ritch at the New York Eye & Ear Infirmary has shown that volunteers who take ginkgo biloba improve the circulation to their eye by 24%. Other researchers are now looking at that in the glaucoma population.”

When prescribing a ginkgo biloba supplement, Dr. Abel said that he prefers a liquid preparation to pill form. He recommends 15 drops of the liquid, with a glass of water, twice a day to patients for superior absorption. “The liquid is absorbed very well and does not depend on stomach acid,” he said. “Many people have poor digestion and may not be getting all of their nutrition, including the vitamin supplements, so I recommend that they take their vitamins in capsules whenever possible.”

Dr. Bartlett said that the supplement may offer hope to patients who have undergone many of the conventional treatments already without much luck. “I have recommended ginkgo biloba to a few patients, most with normal-tension glaucoma and mostly after they have already had filtering surgery,” he said. “If they continue to lose visual fields and lose optic nerve tissue despite the fact that I have them on maximum medical therapy and they’ve already had glaucoma filtering surgery, there isn’t a whole lot left to offer those patients. So in a select population and a very small percentage of glaucoma patients, I will make some recommendations in that regard.”

Note other medications

Of course, the practitioners agreed that ginkgo biloba — as is the case with any supplements or medications — should be prescribed only after taking a thorough history of any other medications the patient may be taking. “Ginkgo biloba does have some risks,” Dr. Bartlett cautioned. “It is an anticoagulant agent, and if patients are taking vitamin E, aspirin, Coumadin (crystalline warfarin sodium, DuPont) or anything else that thins the blood, there can be some risk of hemorrhage. In fact, there have been some reported cases of ocular hemorrhage and intracranial hemorrhage related to ginkgo biloba therapy.”

Vitamin C: IOP reduction?

Vitamin C supplementation may have a positive effect on the trabecular meshwork, said Dr. Abel, by re-supplying electrons to the fixed-cell membranes, although he did not know of related studies. “In animals,” he said, “it has been found that omega-3 fatty acids, DHA, may lower the pressure 2 to 3 mm Hg at the trabecular meshwork level. So some may have a role, either directly or indirectly, in this flow of pressure.”

While the vitamin may have some effect on lowering intraocular pressure (IOP), it may take a substantial amount to achieve the desired effect, said Leo P. Semes, OD, associate professor of optometry at the University of Alabama at Birmingham. “Some older studies conducted in Italy found that using very high doses of vitamin C — about 28 g a day, an enormous dosage — seemed to help lower the IOP,” he said. “At a dosage over about 5 g a day, one of the biggest side effects of vitamin C is gastrointestinal distress that results in diarrhea, so those dosages are really not viable. That was about 10 years ago, and no one has really pursued that very far since.”

Benefits of other vitamins

Addressing some of the nutritional deficiencies in older patients may aid in glaucoma treatment as well, said Dr. Abel. All of the B vitamins, such as B-12, and magnesium may help fortify the optic nerve, he said. “People can take 1,000 mcg under their tongue,” he said. “Alpha lipoic acid has sulfur in it and is a nerve supporter. Also, a general multivitamin is necessary to give people that extra sprinkle of A, C and E, and it is hoped it will have lutein in it, some zinc and some taurine.”

A more unusual all-natural supplement, Dr. Abel suggested, is the Indian and Nephali herb called Triphala, a mild laxative that temporarily lowers IOP and even aids in blood flow to the eye. “It reduces stress because it relaxes you,” he said. “It is ironic to think of a laxative helping your eyes, but in the 16 people we tested, most people had reduced eye pressure for 1 to 6 months. All of them said they just felt better in general, and that’s part of relaxation — a way to enhance and support microcirculation.”

One supplement that may have an effect on nitrous and nitric oxide regulation is L-arginine, an amino acid that may be purchased over the counter, said Dr. Semes. “The dosage of that has to be very carefully controlled,” he said. “So that’s still up in the air, and nobody’s really sure what the human potential is.”

Also helpful are carotenoids for general vision health and lutein for building the pigment layer in the retina, said Dr. Abel.

He noted that artificial sweeteners, such as aspartame, might contribute to retinal toxicity as well as have a detrimental effect on the rest of the body. “People may not realize that artificial sweeteners are neurotoxic; that’s why your tongue tingles and you have a funny taste that lasts a while,” he said. “Your body can’t degrade them. It’s one of those hidden secrets: if you have glaucoma or have a tendency for it, you don’t want to add insult to injury.”

Exercise for the eyes

Another way to improve vascular status is through exercise, which improves blood flow, reduces exertion on the heart and enhances breathing. While exercise may help in the battle against glaucoma by lowering IOP slightly, said Dr. Bartlett, it must be done consistently to reap the most benefit. “If patients do it for a while and stop, they will experience a reversal of that beneficial effect,” he said. “It’s not something that a lot of elderly glaucoma patients are likely to do anyway.”

Exercise does not have to be strenuous to benefit the patient, said Dr. Abel. Using low-impact exercises, such as the Chinese martial art Tai-Chi, he said, and a Chinese breathing exercise called Chi-Kung, can help decrease stress. “I look at glaucoma as a disease of stress: many of the medicines that are employed to treat glaucoma have something to do with adrenaline or epinephrine, which is the neurotransmitter for the sympathetic nerve system,” he said. “By reducing stress, you reduce building up your free radicals, and, therefore, your antioxidant supply is not reduced. Good nutrition is useful for building up your antioxidant level for wherever it’s needed. Rather indirectly, it’s useful for helping your nerve fibers in glaucoma.”

Traditional therapy

In the traditional medical therapy arena, Dr. Bartlett said that Xalatan (latanoprost ophthalmic solution .005%, Pharmacia & Upjohn) is becoming more and more popular as first-line therapy. He cited ease of use and lack of systemic side effects as primary reasons for widespread use. “It has no cardiac effects, no pulmonary effects and no central nervous system effects. It’s really very safe,” he said. “Xalatan is easy to use and is as good as, or perhaps even better than, beta-blockers in some patients.”

Whereas the effectiveness of many medications tends to diminish over time as the patient builds up immunity to a drug, said Dr. Abel, the effect of Xalatan remains constant. “Xalatan is becoming more frequently used because its effect appears to remain the same over the months,” he said. “You don’t see a decrease in its effect, and it doesn’t depend on outflow or on the production of aqueous like other drugs do; it uses uveoscleral outflow.”

Points of caution

Dr. Bartlett said that, while it is difficult to predict what the IOP response will be, whether or not the patient will experience iris pigmentation change is relatively easy to determine depending on the patient’s iris color configuration. Hypertrichosis, or increased lengthening, thickening or darkening of the eyelashes, is another documented side effect. There have been a few anecdotal reports, but nothing conclusive, indicating that pseudodendrite formation is a potential complication as well, he noted. “Other than that, there’s really no ocular concern at all,” he said.

One instance in which precautions should be taken is with the newly postoperative eye, Dr. Abel noted, when potential for inflammation may cause redness. The frequency of uveitis or cystoid macular edema is quite low, he added.

Another alternative is Alphagan (brimonidine tartrate 0.2%, Allergan), said Dr. Bartlett. Practitioners can expect the same IOP-lowering efficacy as from a beta-blocker, he said, with few side effects, which include dry mouth, dizziness and, more frequently, allergy. “Perhaps 10% of patients will develop an allergy, maybe a contact dermatitis around the eye or contact conjunctivitis as a response,” he said. “Most patients can tolerate it quite well.”

While brimonidine may seem a safe alternative, said Dr. Semes, it, too, should be used with caution. “I think we’re going to find that there are some side effects with agents such as brimonidine — things that were discovered later in the process with beta-blockers. It’s a little premature to completely go with some of these alternative strategies,” he said.

Role of beta-blockers

Some practitioners prefer beta-blockers as a first choice despite concern about possible systemic side effects. However, Dr. Abel said, the potential side effects make practitioners look to available alternatives.

“Beta-blockers are reasonably inexpensive, available and selective, and as little as one drop a day can reduce pressure in the younger individual,” he said. “But one has to constantly ask these patients about their breathing and heart rate. For elderly patients, going with a carbonic anhydrase inhibitor, such as Azopt (brinzolamide 1%, Alcon) or Trusopt (dorzolamide, Merck), or Xalatan may be more appropriate.”

Carbonic anhydrase inhibitors

While systemic carbonic anhydrase inhibitors may have many systemic side effects, said Dr. Semes, the topical form does not, although its effectiveness is unpredictable. “The carbonic anhydrase inhibitors are ineffective, in my experience, in about 50% of the cases,” he said. “It just seems that some patients happen to do better with them, and it’s a try-and-see approach.”

Using Cosopt (dorzolamide HCl-timolol maleate, Merck), the combination of Trusopt and the beta-blocker timolol maleate, helps with convenience and, therefore, may improve a patient’s compliance, said Dr. Bartlett. However, he prefers Azopt to other carbonic anhydrase inhibitors.

“We did some studies of Azopt before it was approved by the Food and Drug Administration, and we found, as others have found, that it’s very comfortable compared to Trusopt; it doesn’t sting as much,” he noted. “When used by itself, it can be used twice a day, whereas Trusopt really has to be used three times a day in monotherapy. I typically don’t use topical carbonic anhydrase inhibitors as first-line therapy — they’re not as effective as beta-blockers or Alphagan or Xalatan. But when patients have a contraindication to a beta-blocker, or you’ve tried Alphagan and the patient develops an allergy to it, then I consider the carbonic anhydrase inhibitors as a third-line choice.”

The future of neuroprotection

While there is much basic research being conducted in the area of neuroprotection, Dr. Bartlett said that there is no firm clinical evidence that Alphagan or Betoptic S (betaxolol HCl 0.25%, Alcon) may have neuroprotective activities, and he and Dr. Semes caution against “jumping on the neuroprotection bandwagon.” Looking at the role of nitric oxide and glutamate antagonists in preserving optic nerve tissue or retinal ganglion cells, he said, may hold promise for future treatment. “It’s a really exciting avenue for research,” Dr. Bartlett said. “Over the next several years, some medications may come on the market to protect optic nerve tissues. There’s a lot of excitement in the glaucoma area; there’s always something new in terms of therapy and intervention.”

For Your Information:

Jimmy D. Bartlett, OD, is a director of residency programs and fellowships at the School of Optometry and a professor of pharmacology in the School of Medicine at the University of Alabama at Birmingham. He can be reached there at 1716 University Blvd., Birmingham, AL 35294-0010; (205) 934-3036; fax: (205) 934-6758. Dr. Bartlett has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Rob Abel, MD, is the author of the Eye Care Revolution, and he has a Web site, www.eyeadvisor.com. He may be reached at Delaware Ophthalmology Consultants, 3501 Silverside Rd., Wilmington, DE 19810; (302) 479-3937; fax: (302) 477-2650. Dr. Abel has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned. He is on the Kemin Foods Lutein Advisory Board.

Leo P. Semes, OD, is an associate professor of optometry, University of Alabama at Birmingham and a member of the Primary Care Optometry News Editorial Board. He may be contacted at 1716 University Blvd., Birmingham, AL 35294-0010; (205) 934-6773; fax: (205) 934-6758; lsemes@icare.opt.uab.edu. Dr. Semes has no direct financial interest in the products mentioned in this article. He is a paid consultant for Alcon.